Most cases of paediatric HIV now occur during the breastfeeding period. Through an EDCTP-2 funded randomized controlled trial in Burkina Faso and Lusaka, we tested a postnatal prevention strategy relying on point of care (POC) early infant diagnosis (EID) and maternal VL tests for same-day infant lamivudine initiation when VL>1000 copies/mL until the end of breastfeeding, and maternal ART optimization. At the 2nd immunization visit (EPI-2), maternal HIV status was reassessed and infants from HIV-positive mothers were enrolled. Among the 754 children in each arm, the 12-month transmission rate was 1.16/100pers-yrs (CI:0.44-2.60) in the control arm vs. 0 (97.5%CI: 0.71) in the intervention arm. The period at risk for infant (i.e.HIV VL>1000c/mL and no prophylaxis) was 5.96/100pers-days (95%CI: 5.85-6.1) vs. 0.36 (95%CI: 0.34-0.36). The primary objective of the proposal is to assess the effectiveness of a similar intervention in 2 provinces of Zambia, to reach zero postnatal transmission. For this implementation research proposal, we will use the RE-AIM framework. We designed a cluster randomized controlled arm with 2000 HIV-exposed HIV-negative children (1000 per arm) recruited at EPI-2 visit, in 40 clusters (maternal & child health centres) matched for district and size. The primary trial outcome is postnatal HIV infection at 18 months. The EID and VL tests will be organised at the district level with a mobile team equipped with POC machines, and one referral MCH centre equipped with Xpert platform. Research capacity will be built through PhD fellowships. By demonstrating the (cost)-effectiveness of POC tests and infant lamivudine (health technologies) to prevent infant HIV infection, identifying and addressing barriers to uptake in RE-AIM, notably via end-users participation, and ensuring the translation of research findings into policy through the strong involvement of policy makers, this study addresses both objectives of EDCTP-3 and those of the present call.

Childhood tuberculosis (TB) remains globally underdiagnosed and untreated. In 2022, WHO conditionally recommended the use of treatment decision algorithms (TDAs) to improve the diagnosis of pulmonary TB in children <10 years and called for the external validation of two suggested TDAs for children. The Decide-TB project aims to generate evidence for the implementation of a comprehensive TDA-based approach for TB in children living in high-burden, resource-limited countries, at district hospital and primary health centre levels, and to facilitate the integration of this evidence into practice and policy. As an interdisciplinary consortium of researchers and national TB programs (NTPs), we will conduct a programmatic pilot of WHO-suggested TDAs, also integrating specific TDAs for children living with HIV and/or those malnourished, and severity assessment for shorter treatment decision in non-severe TB disease. Clinical mentoring tools and a Clinical Decision Support System will be developed. District information systems will be strengthened to collect individual data for program monitoring and supervision by NTPs, and for research. The TDA-based approach will be tested in a pragmatic stepped wedge cluster-randomized trial, including effectiveness, implementation, socio-behavioural, economics and policy research components. The diagnostic accuracy of TDAs will be assessed in a parallel meta-analysis of children with presumptive TB from recent studies led by consortium members. The pragmatic trial and meta-analysis will contribute to external validation of the WHO-suggested TDAs. Engagement of key stakeholders and decision-makers throughout the project will support adoption into international and national policies and into clinical practice. Through validation of TDAs, widespread policy adoption, and translation into clinical practice, Decide-TB will increase access to safe and effective TB management for children, thus reduce TB mortality and contribute to SDG3.

Malaria is a life-threatening disease causing more than 500,000 deaths every year in sub-Saharan Africa. Prevention of the disease is best achieved by vector control which relies on the use of insecticides. Monitoring mosquito vector populations is an integral component of control programmes and a prerequisite for effective interventions. Several individual methods are used for this task, However, there are obstacles to their uptake, as well as challenges in organizing, interpreting and communicating vector control data. We will develop a fully integrated and automated multiplex vector-diagnostic platform (LabDisk) for monitoring the species ID, the infection status of mosquitoes and the insecticide resistance profile of malaria vector populations. The system will provide sample-to-answer determinations, and it will perform genotyping at substantially lower cost, compared to the assays that are currently used in Africa. The LabDisk will be interfaced with a Disease Data Management System (DDMS), custom made data management software which will collect data from routine entomological monitoring activities, store, and make available stratified information based on “user queries” in a standardized way. The “GAME”, a modern ICT platform that employs interactive ways of communicating guidelines and exemplifying good practices of successful use of interventions in the health sector will be also employed, to teach operational end users the use of data to make informed decisions. The integrated system (LabDisk, DDMS & Game) will be implemented in four sub-Saharan African countries, highly representative of malaria settings and vector control problems, to support informed decision-making about vector control and disease management. It will cover the urgent needs of an existing “market” and will provide solution to end users, to address a most important societal challenge in Africa, the control of malaria. The system has a vast expansion potential in other applications.